We intend to examine the cytotoxic effect of various chemotherapeutic agents both alone and in combination, on murine plasmacytomas. A number of new agents of interest to us from the NCI screening program will be investigated as will the alkylating agents such as cyclophosphamide, melphalan and BCNU which have been shown to be effective against human myelomas and the antimetabolites such as cytosine arabinoside and 5-fluorouracil which have demonstrated little clinical activity. Initial study will involve increase in lifespan as an endpoint; this will allow us to quickly define sensitivity and resistance of the tumors to different anticancer agents. The spleen colony assay will be used for further quantitation of clonogenic plasmacytoma cells. We will examine the relationship between sequence and interval of drug administration and the effectiveness of a number of two-drug combinations such as cyclophosphamide-BCNU and melphalan-prednisone. The data we obtain on single agents, fractionated regimens, and combination therapy will be applied to curative strategies against murine plasmacytomas and eventually to clinical protocols. A major effort will be made to define patterns of resistance to drugs in naturally-occurring and drug selected mutants and an attempt will be made to define and then overcome such resistance. The cell kinetics of MOPC-315 plasmacytoma will be studied in order to clarify the relationship between clonogenic cells as measured by spleen colony assay, paraprotein synthesizing cells measured by a modified Jerne plaque assay, and plasma immunoglobulin levels measured by a hemagglutinin assay. This will be done as a function of tumor growth and drug treatment.